A Microfluidic Platform for the Rapid Determination of Distribution Coefficients by Gravity-Assisted Droplet-Based Liquid鈥揕iquid Extraction

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• 作者：Carl Esben Poulsen ; Robert C. R. Wootton ; Anders Wolff ; Andrew J. deMello ; Katherine S. Elvira
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：June 16, 2015
• 年：2015
• 卷：87
• 期：12
• 页码：6265-6270
• 全文大小：325K
• ISSN：1520-6882

文摘

The determination of pharmacokinetic properties of drugs, such as the distribution coefficient (D) is a crucial measurement in pharmaceutical research. Surprisingly, the conventional (gold standard) technique used for D measurements, the shake-flask method, is antiquated and unsuitable for the testing of valuable and scarce drug candidates. Herein, we present a simple microfluidic platform for the determination of distribution coefficients using droplet-based liquid鈥搇iquid extraction. For simplicity, this platform makes use of gravity to enable phase separation for analysis and is 48 times faster and uses 99% less reagents than performing an equivalent measurement using the shake-flask method. Furthermore, the D measurements achieved in our platform are in good agreement with literature values measured using traditional shake-flask techniques. Since D is affected by volume ratios, we use the apparent acid dissociation constant, pK鈥? as a proxy for intersystem comparison. Our platform determines a pK鈥?value of 7.24 卤 0.15, compared to 7.25 卤 0.58 for the shake-flask method in our hands and 7.21 for the shake-flask method in the literature. Devices are fabricated using injection molding, the batchwise fabrication time is <2 min per device (at a cost of $1 U.S. per device), and the interdevice reproducibility is high.